While Dr. Cartsos and colleagues are to be commended for their January JADA study of adverse jaw outcomes in a medical claims database of 15 million lives, the study methodology renders many of their conclusions problematic ("Bisphosphonate Use and the Risk of Adverse Jaw Outcomes: A Medical Claims Study of 714,217 People" (JADA 2008; 139[1]:23–30).
The authors set out to define the risk of developing osteonecrosis of the jaw (ONJ) among 714,217 people who were receiving oral or intravenous (IV) bisphosphonates. The diagnostic and procedure codes used as a basis for their findings are far too broad to allow any conclusions to be drawn about ONJ as an entity. Because no International Classification of Diseases, Ninth Revision, code for ONJ is available, they used codes for inflammatory conditions of the jaws, major jaw surgery necessitated by necrotic or inflammatory indications, and jaw surgeries necessitated by a malignant process.
- – Inflammatory conditions of the jaws may include ONJ but also many other conditions, including infections such as osteomyelitis. Accepted definitions of ONJ put forth by expert panels from the American Association of Oral and Maxillofacial Surgeons1 and the American Society for Bone and Mineral Research2 are far narrower and more exclusive.
- – Major surgeries for a necrotic or inflammatory process of the jaw are problematic for capturing ONJ cases for a similar reason. The conditions necessitating such surgeries encompass a broader range of processes than what most experts would consider ONJ.
- – Jaw surgeries necessitated by a malignant process is a category that would be explicitly excluded under all accepted definitions of ONJ. Patients with cancers of the jaw or who have received radiotherapy for head and neck cancers should be excluded from consideration as true ONJ cases because the malignant process itself, or the radiotherapy itself, may have caused the lesion.
Because the authors are unable to confirm diagnoses by chart review, it is impossible to validate the frequency estimates for the occurrence of ONJ using accepted definitions in patients receiving IV versus oral bisphosphonates or in patients with cancer compared with patients with osteoporosis. Without being able to apply accepted definitions of ONJ systematically to each case reviewed in this study, one cannot use these study findings to inform clinical treatment decisions in patients considered to be at risk of developing ONJ owing to their disease state or the type of bisphosphonate they are receiving.
The database used studied patients from 2000 to 2006, when no U.S. Food and Drug Administration–approved IV bisphosphonate was available for treatment of osteoporosis; yet they found 1,800 patients treated with IV bisphosphonates for osteoporosis, raising concerns that some of these patients may have had osteoporosis and cancer. Looking at the diagnoses and medications of these patients in the six months prior to the prescription for bisphosphonates may be helpful in further understanding the authors’ results.
The authors conclude that use of oral bisphosphonates had a protective effect on ONJ. Unfortunately, the authors did not correct for multiple comparisons.
Although the authors are careful to apply their findings to "adverse jaw outcomes" in patients treated with bisphosphonates, the data should not be misread as applying to ONJ. Because the role of bisphosphonates in the development of ONJ is not well-understood, and because the risk factors for ONJ are multifactorial in nature, it is even more difficult to surmise the role, if any, that bisphosphonates may have had in contributing to any of the adverse jaw outcomes reported in this retrospective database review.
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